Clostridium difficile infection ( CDI ) in children ( <16 years of age )
|Publication: 08/09/2016 --|
|Last review: 01/01/1900|
|Next review: 08/03/2020|
|Approved By: Improving Antimicrobial Prescribing Group|
|Copyright© Leeds Teaching Hospitals NHS Trust 2016|
This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
Diagnosis and management of Clostridium difficile infection (CDI) in Children (<16 years of age)
Clostridium difficile is a spore-forming, obligate anaerobic, Gram-positive bacillus and is acquired from the environment or by the faecal-oral route. Some strains produce toxins A and B which are responsible for intestinal disease. C. difficile is a cause of antimicrobial-associated diarrhoea and is a common health care-associated pathogen.
Clinical symptoms vary widely, from asymptomatic colonization, through mild diarrhoeal illness to pseudomembranous colitis with bloody diarrhoea, fever, and severe abdominal pain. Poor outcomes (intensive care admission, colectomy or death) do occur in children with CDI but these are uncommon, occurring in 2% in a recent Canadian series.1 Healthy neonates are frequently colonised by C. difficile and these strains may produce toxin without it causing disease. In a study of community samples in Oxfordshire colonisation rates in asymptomatic children under 30 months were approximately 20%.2
Presumed factors that increase the risk of acquiring CDI in children:3
CDI usually requires specific treatment to reduce the duration of symptoms and the risk of spread (see Empirical antimicrobial therapy).
Recommendation: Symptoms or clinical signs cannot be used to reliably distinguish CDI from other causes of diarrhoea in children.[Evidence level B]
Recommendation: CDI is diagnosis that requires either laboratory confirmation or visualization of pseudomembranes on sigmoidoscopy or colonoscopy. [Evidence level B]
Recommendation: This guideline applies to children 2-16 years old with diarrhoea (at least one type 5-7 stool, Bristol stool chart) and a positive CDI result (both positive glutamate dehydrogenase (GDH) and positive toxin assays)
Recommendation: Avoid routine testing for CDI in children younger than 2 years (carrier state rate is highest in this age group) and consider other causes of diarrhoea, particularly viruses.
Endoscopic findings of pseudomembranes and hyperaemic, friable rectal mucosa suggest pseudomembranous colitis and are sufficient to diagnose CDI at any age.
For reference, Table 1 summarises the interpretation of Clostridium difficile laboratory test results.
Please see detail.aspx?id=677 to guide when testing is recommended.
Recommendation: All CDI episodes should have the severity assessed and recorded daily in the medical notes (and the initial severity also recorded on the prescription chart.) [Evidence level D]
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Recommendation: Measure serum lactate daily in severe infection, until there are clinical signs of improvement or surgical intervention is required. [Evidence level D]
Only adult data support the recommendation for lactate measurement. In a retrospective analysis of adult intensive care unit admissions, patients with a serum lactate ≥ 5 mmol/L had an increased risk of dying (Adjusted Odds Ratio, 12.4; 95% CI, 2.4-63.7), whereas those with lactate between 2.2 and 4.9 mmol/L appeared to benefit from colectomy.9 As in other causes of severe sepsis, serum lactate can be a useful marker of deterioration requiring surgical assessment. DOH guidelines recommend monitoring lactate in life-threatening infection10, but it may be too late at this point; hence the recommendation for earlier testing.
Patients with C. difficile infection often have diarrhoea, which is profuse, watery and may have a characteristic smell, although none of these clinical features are specific for C. difficile infection and a microbiological diagnosis is required for confirmation.
Recommendation: Children with CDI should be reviewed daily and agreed plans regarding fluid resuscitation, electrolyte replacement and nutrition should be clearly documented in the patient’s notes.10,3 [Evidence level B]
Recommendation: The need for antimicrobials for other indications,7,10 proton pump inhibitors (PPI) and any medicines that can produce diarrhoea should be reviewed (Do not stop PPI where there is a history of gastrointestinal bleeds). [Evidence level B]
Recommendation: Severe CDI or patients with evidence of severe colitis (e.g. guarding, bloody diarrhoea, abdominal tenderness or radiological evidence) require specialist surgical input. Colectomy is required in some patients with megacolon, perforation or septic shock.9,11 [Evidence level B]
Recommendation: In severe infections that are not responding to antimicrobial regimens, intravenous immunoglobulin may be considered in consultation with an infection specialist. Approval of the immunoglobulin will be required (see DTC web pages). [Evidence level B]
|Empirical Antimicrobial Treatment|
While this guideline relates primarily to confirmed cases of CDI, if there is a strong clinical suspicion of severe CDI infection, it is clinically sensible to begin therapy empirically (see below) pending test results.
For those with suspected moderate disease but potential recurrence, it is a clinical decision if to commence therapy empirically (see below), pending test results.
For those suspected of mild disease only, it would usually be appropriate to withhold treatment pending test results.
|Directed Antimicrobial Treatment (when microbiology results are known)|
Recommendation: In all cases the need for (non-CDI) antimicrobials should be reviewed as these are associated with poorer outcome. [Evidence level B]
Recommendation: Risk stratify treatment choices by severity of illness [Evidence level C]
Moderate disease. Metronidazole (Child 1–2 months 7.5 mg/kg every 12 hours, Child 2 months–12 years 7.5 mg/kg (max. 400 mg) every 8 hours,
Child 12–18 years 400 mg every 8 hours, for 10 days : BNFc) or oral vancomycin (Child 1 month–5 years 5 mg/kg 4 times daily for 10 days, Child 5–12 years 62.5 mg 4 times daily for 10 days, Child 12–18 years 125 mg 4 times daily: BNFc ) if no resolution of symptoms or deterioration in severity score. For patients unable to take oral therapy, the IV route can be used, but appears less effective.
Severe disease. Use oral vancomycin (Child 1 month–5 years 5 mg/kg 4 times daily, increased up to 10 mg/kg 4 times daily if infection fails to respond or is life-threatening; Child 5–12 years 62.5 mg 4 times daily, increased up to 250 mg 4 times daily if infection fails to respond or is life-threatening; Child 12–18 years 125 mg 4 times daily, increased up to 500 mg 4 times daily if infection fails to respond or is life-threatening: BNFc) and IV metronidazole, doses as above.
|Switch to oral agent(s)|
This section is rarely relevant to CDI but in children with severe CDI who are commenced on IV Metronidazole , there is no need to change this to oral metronidazole, it can simply be stopped when there is clinical improvement.
Duration of therapy
Recommendation: Diarrhoea should resolve within 1-2 weeks, if diarrhoea has improved but persists at 14 days but the patient is otherwise stable, the WCC is normal, and there is no abdominal pain or distension, the persistent diarrhoea may be not due to infectious cause. [Evidence level D]
Recommendation: Treatment failure should not be assessed before day 7 of therapy . [Evidence level C]
Recommendation: Seek a surgical opinion if symptoms worsen, severity score moves from moderate to severe or serum lactate worsens. [Evidence level C]
Recommendation: Recurrence of CDI is usually defined as recurrence of diarrhoea (at least 3 consecutive type 5-7 stools) and a positive C. difficile toxin assay within 30 days of a previous CDI episode and after resolution of previous symptoms (i.e. no diarrhoea for at least 48 hours).3,16
Recommendation: For first recurrent infection use Oral Vancomycin (40 mg/kg/day in 4 divided doses; maximum, 2 g/day). [Evidence level D]
For multiple recurrences/intractable cases, please see below.
Vancomycin and Metronidazole have similar efficacy for mild CDI, and in children, it was safe to use Metronidazole for moderate infection.8 Vancomycin appears to be superior for more severe infections.12-14 Because of concerns about cost and selection for Vancomycin resistant bacteria (e.g. vancomycin resistant enterococci, particularly in paediatric oncology patients) and a lack of superiority of Vancomycin for mild infection, Metronidazole is the recommended first line agent in this situation.3,5,7,8 Oral therapy is generally preferred to intravenous therapy because the pathogen, and thus the source of toxin production, is located in the bowel lumen; however, intravenous Metronidazole also reached bactericidal concentrations in faeces.15 There is no robust evidence that higher doses of Vancomycin (e.g. up to 2g/day) are more efficacious than lower doses in severe infection in adults, and standard 125mg dosing provides more than adequate stool concentrations), hence the dosing recommendation for severe infection. However, if there is evidence of ileus then, in severe infection, an increased dosage of oral vancomyin (up to 500mg four times daily) may be prudent. Intravenous therapy is advised in addition to oral/ng therapy in severe infection because impaired gut motility may slow/impair delivery of the antimicrobials to the site of infection.
The management of intractable cases and multiple recurrences is challenging and consultation with individuals experienced in managing these cases is advised. Investigational agents have been used with varying degrees of success
Beyond the use of Metronidazole and vancomycin as above, other therapies should only be considered on a case-by-case basis and in consultation with an infection specialist (microbiology or infectious diseases).
Second or later recurrences
An acceptable tapered regimen is as follows:
Intravenous immunoglobulin may be appropriate (in consultation with microbiology/infectious diseases and the immunoglobulin review panel) in cases of recurrence in patients with low/deteriorating serum albumin.18 Tapering doses of Vancomycin have been used to treat CDI recurrence and remain an option but the regimens have not been standardized or fully evaluated.3
Donor stool transplants (Faecal microbiota transplantation) are occasionally required but this is an area requiring specialist input.
Fidaxomicin has been used in adults with CDI with comparable cure rates and some evidence of reduced recurrence rates in two randomised trials, overviewed by the NICE appraisals group.16 The use of this agent in children is based on one case report19 and a small safety evaluation and pharmacokinetic study20 and cannot be recommended as routine practice; however, in very specific cases it may be justified only after discussion with specialist in microbiology/ infectious diseases and appropriate permissions obtained from the Trust Drugs & Therapeutics group. An example of situation where this off licence use might be considered, would be a severe CDI case (where oral metronidazole is associated with worse clinical outcomes) with concurrent VRE infection or in the context of a VRE outbreak where it would be prudent to restrict oral vancomycin use.
NB. Death certification.21
Clostridium difficile infection
|Target patient group:||Paediatric patients with Clostridium difficile infection|
|Target professional group(s):||Secondary Care Doctors
1. Schwartz KL, Darwish I, Richardson SE, Mulvey MR, Thampi N. Severe clinical outcome is uncommon in clostridium difficile infection in children: A retrospective cohort study. BMC Pediatr. 2014;14:28
4. Epidemiology of Clostridium difficile Infection Daryl D. DePestel, David M. Aronoff J Pharm Pract. 2013 October ; 26(5): 464–475. doi:10.1177/0897190013499521.
6. Shim JO. Clostridium difficile in Children: To Treat or Not to Treat? Pediatric Gastroenterology, Hepatology & Nutrition. 2014;17(2):80-84. doi:10.5223/pghn.2014.17.2.80.
7. Schutze, G. E., Willoughby, R. E., Brady, M. T., Byington, C. L., Davies, H. D., Edwards, K. M., & Zaoutis, T. E. (2013). Clostridium difficile infection in infants and children. Pediatrics, 131(1), 196-200.
8. Pai S, Aliyu SH, Enoch DA, Karas JA (2012) Five Years Experience of Clostridium difficile Infection in Children at a UK Tertiary Hospital: Proposed Criteria for Diagnosis and Management. PLoS ONE 7(12): e51728. doi:10.1371/journal.pone.0051728
9. Lamontagne, F., et al., Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg, 2007. 245(2): p. 267-72.
12. Zar, F.A., et al., A comparison of vancomycin and metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis, 2007. 45(3): p. 302-7.
13. Wilcox, M.H. and R. Howe, Diarrhoea caused by Clostridium difficile: response time for treatment with metronidazole and vancomycin. J Antimicrob Chemother, 1995. 36(4): p. 673-9.
14. Musher, D.M., et al., Relatively poor outcome after treatment of Clostridium difficile colitis with metronidazole. Clin Infect Dis, 2005. 40(11): p. 1586-90.
15. Bolton, R.P. and M.A. Culshaw, Faecal metronidazole concentrations during oral and intravenous therapy for antibiotic associated colitis due to Clostridium difficile. Gut, 1986. 27(10): p. 1169-72.
20. Pam Sears, Sheldon L. Kaplan, Marian Michaels, Shawn Flanagan, and Molly O'gorman. LB-8 A Safety and Pharmacokinetic Study of Fidaxomicin in Children with Clostridium difficile-associated diarrhea Open Forum Infect Dis (Fall 2014) 1 (suppl 1): S69 doi:10.1093/ofid/ofu083.08
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.
D. Leeds consensus. (where no national guidance exists or there is wide disagreement with a level C recommendation or where national guidance documents contradict each other)
Improving Antimicrobial Prescribing Group
LHP version 1.0
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